We will use the LTQ-Orbitrap Elite (a linear ion-trap-orbital ion-trap hybrid mass spectrometer) to support a range of basic, translational, and clinical cancer research projects at the University of Texas M. D. Anderson Cancer Center (MDACC) and in collaborative studies in the Texas Medical Center (TMC). The Orbitrap Elite features include high mass resolution (>240,000), large space charge capacity, high mass accuracy (<3 ppm), a mass/charge range of up to 4000 m/z, and dynamic range greater than 103. The documented performance of the Orbitrap Elite exceeds that of most alternative instruments in three critical areas by at least one order of magnitude-resolution, mass accuracy, and scan speed. Those improvements make the Orbitrap the optimal mass spectrometer for proteomic and metabolomic platforms aimed at identification and validation of molecular markers. Its high-resolution, accurate mass capabilities previously could only be achieved with superconducting magnet systems. Importantly, those capabilities have made extraordinary contributions to the analysis of protein complexes, post-translational modifications, and biomarker discovery (identification of previously unidentified proteins and metabolites) as well as early-stage validation studies. The Orbitrap is especially suitable for studies employing stable isotope-dilution mass spectrometry or label-free quantification of proteins or metabolites. We expect that using the Orbitrap for molecular identification studies will imminently improve the diagnosis, treatment, and prognosis of human cancers, in keeping with the goal of the Kleberg Center for Molecular Markers (where the Proteomics Facility is housed) to improve the outcomes of cancer patients. We will use the proposed Orbitrap Elite in support of at least 7 NIH-funded R01, P01, and SPORE grantees and eventually many other NIH-funded projects at MDACC as well as in the TMC. Specifically, we plan to apply this new, improved mass spectrometer to the discovery of protein biomarkers in ongoing projects in breast, brain, ovarian, and prostate cancers. By identifying and validating such biomarkers and helping to identify new drug targets, the instrument will help us improve public health through improvements in the diagnosis and treatment of cancer. It will complement our functional proteomics-based personalized medicine initiatives in the Kleberg Center for Molecular Markers and eventually improve treatment of the large number of cancer patients treated each year at MDACC, the largest and top ranked cancer center in the United States.